Comstock is known as the Prophet of Columbia. In addition to founding the city, he is revered as the leader of its religion and looked at by citizens as though he's God. In order to attain his lofty position as a prophet, he predicts future events by looking through tears opened by Rosalind Lutece which show him the most likely future. As explained in the fictional Truth from Legend documentary, Comstock "championed the Founding Fathers of America with an almost religious fervor." [1]

When Booker DeWitt arrives in Columbia, it is revealed that Comstock was expecting his arrival, however he had predicted it to occur at a later date. He warns the city of this "false shepard" and asks anyone to report a man with the initial A.D. on his hand. He aspires to keep Elizabeth away from Booker at all cost, sending various enemies and obstacle to hinder Booker's objective.

Comstock has suffered his own personal tragedy, when his wife (the First Lady of Columbia) was allegedly murdered by Daisy Fitzroy. It is later revealed that he himself ordered the murder and pinned it on Fitzroy who was a housekeeper for him at the time.

Due to his extensive exposure to the Lutece's tear technology, not only has Comstock become sterile, but he is also suffering from numerous physical complications accounting for how much older he appears than Booker despite the fact that they are the same age.

As you reach the final chapters of the game it is revealed that Comstock is the born again Booker DeWitt, one who accepted his baptism after his battles at Wounded Knee. Comstock later meets with either Rosalind or Robert Lutece depending on which universe he is in and funds their research into quantum levitation in order to make Columbia a reality. It is with the help of the Lutece twins that he also learns of transdimensional travel and the outcomes of his lives in which he doesn't accept the baptism, finds a wife and has Anna DeWitt. With the help of the Luteces he is able to trick Booker into giving up his daughter under the pretense of erasing his gambling debt. The Luteces open up a tear into Bookers universe in order to bring Anna and Robert across. However, Booker has second thoughts and arrives to try to get his daughter back. He tries to prevent Comstock from taking Anna through the tear but the only result of his struggle is that Anna's pinky finger is sheared off by the closing tear, resulting in her gaining extradimensional powers. This is where Elizabeth comes from as the seed of the prophet and with this knowledge the Lady Comstock accuses Comstock of an affair with Rosalind Lutece.

In the timeline that eventually leads to thed destruction of New York, Comstock captures and brainwashes Elizabeth, shaping her in his own image and turning her into the zealous leader he himself had been.

Comstock is finally killed near the end of the game by Booker after he rescues Elizabeth. They fight their way onto his flagship The Hand of the Prophet and confront him. He dies after having his head smashed against a fountain and drowned in it.

To give you more background here is the first instance you meet Comstock in person.